Review: the role of automation in improving the performance and throughput of microsample bioanalysis

Background: Microsampling is one of the most dynamic and rapidly evolving topics in bioanalysis. It can provide numerous advantages in comparison to traditional biological fluid sampling (safety and analyte stability, feasible shipping, lower storage expenses and increased environmental friendliness). All these advantages can be put to ideal use if microsampling is coupled to advanced automation. Most modern microsampling techniques are designed for optimal automatability of the sampling procedure, or of any of the subsequent analytical workflow steps, so that the usual advantages of the former can be enhanced by increased throughput, better safety and lower per-analysis expenses. However, finding relevant information on recent advances in automation for the bioanalysis of microsamples is still a challenging task. Results: In this review paper with 91 references, the most recent and relevant applications of full automation and semi-automation in biological microsample analysis are presented, with notes on the advantages and limitations of each approach. Some less recent examples are also presented, providing context or insight into the evolution of subsequent developments. This unique approach allows a better understanding of the close intertwining and complementarity of microsampling, automation and miniaturised sample preparation, an integration that is essential to ensure optimal and reliable results. Differences between classical and advanced microsampling techniques regarding their performance related to overall process automation are clearly laid out. Ample space is reserved for discussion on the most recent trends and what the authors believe will be the most important future developments. Significance: This review paper shows for the first time how coupling microsampling to analytical workflow automation could be the tipping point that will help microsampling become fully established in routine bioanalysis. Most disadvantages of microsampling can be either alleviated, outright solved or made irrelevant by automation, and this unprecedented development has the potential to revolutionise an entire research and application field. This is true in most use cases, including therapeutic drug monitoring, forensics, anti-doping and preclinical, clinical and toxicological studies.